Antibodies to .beta.-amyloids or their derivatives and use there

Details Antibodies to .beta.-amyloids or their derivatives and use there Antibodies to .beta.-amyloids or their derivatives and use there

1994-09-15

1998-05-12

Hutzell, Paula K.

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving antigen-antibody binding, specific binding protein...

435 792, 435 794, 435 795, 435 7021, 435326, 435331, 5303879, 5303881, 5303891, G01N 3353

Patent

active

057503494

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

The present invention relates to antibodies which are useful and novel in that they have binding specificity to .beta.-amyloids or their derivatives. More particularly, the present invention relates to antibodies useful for the development of assays of .beta.-amyloids or their derivatives based on antigen-antibody reaction, diagnoses of diseases to which .beta.-amyloids or their derivatives are related (for example, Alzheimer's disease), or the development of preventive-therapeutic compositions for Alzheimer's disease.


BACKGROUND ART

Senile dementia caused by Alzheimer's disease has raised a serious social problem, and the early establishment of diagnoses and therapeutic methods of Alzheimer's disease has been desired. As lesion characteristic of the brains of patients with Alzheimer's disease, the excessive formation of senile plaques and neurofibrillary tangles have been known. Of these, one of the main constituents of the senile plaque is a .beta.-amyloid or a derivative thereof.
The .beta.-amyloid is a peptide composed of about 40 amino acids, and is coded in the vicinity of the transmembrane region of an amyloid precursor protein (hereinafter referred to as an APP). Amino acid sequences of the .beta.-amyloids are shown below:


__________________________________________________________________________ Amyloid (1-38)! SEQ ID NO: 1 Asp--Ala--Glu--Phe--Arg--His--Asp--Ser--Gly--Tyr--Glu--Val--His-- His--Gln--Lys--Leu--Val--Phe--Phe--Ala--Glu--Asp--Val--Gly--Ser--Asn-- Lys--Gly--Ala--Ile--Ile--Gly--Leu--Met--Val--Gly--Gly Asp--Ala--Glu--Phe--Arg--His--Asp--Ser--Gly--Tyr--Glu--Val--His-- His--Gln--Lys--Leu--Val--Phe--Phe--Ala--Glu--Asp--Val--Gly--Ser--Asn-- Lys--Gly--Ala--Ile--Ile--Gly--Leu--Met--Val--Gly--Gly--Val Asp--Ala--Glu--Phe--Arg--His--Asp--Ser--Gly--Tyr--Glu--Val--His-- His--Gln--Lys--Leu--Val--Phe--Phe--Ala--Glu--Asp--Val--Gly--Ser--Asn-- Lys--Gly--Ala--Ile--Ile--Gly--Leu--Met--Val--Gly--Gly--Val--Val Asp--Ala--Glu--Phe--Arg--His--Asp--Ser--Gly--Tyr--Glu--Val--His-- His--Gln--Lys--Leu--Val--Phe--Phe--Ala--Glu--Asp--Val--Gly--Ser--Asn-- Lys--Gly--Ala--Ile--Ile--Gly--Leu--Met--Val--Gly--Gly--Val--Val--Ile Asp--Ala--Glu--Phe--Arg--His--Asp--Ser--Gly--Tyr--Glu--Val--His-- His--Gln--Lys--Leu--Val--Phe--Phe--Ala--Glu--Asp--Val--Gly--Ser--Asn-- Lys--Gly--Ala--Ile--Ile--Gly--Leu--Met--Val--Gly--Gly--Val--Val--Ile--Ala Asp--Ala--Glu--Phe--Arg--His--Asp--Ser--Gly--Tyr--Glu--Val--His-- His--Gln--Lys--Leu--Val--Phe--Phe--Ala--Glu--Asp--Val--Gly--Ser--Asn-- Lys--Gly--Ala--Ile--Ile--Gly--Leu--Met--Val--Gly--Gly--Val--Val--Ile-- Ala--Thr __________________________________________________________________________
According to recent reports, some of the patients with familial Alzheimer's disease belong to families having point mutations on APP, and the possibility has been pointed out that the .beta.-amyloids are one of the causative substances for Alzheimer's disease. Based on such a background, the .beta.-amyloids have been intensively studied as a main subject for the investigation of Alzheimer's disease, and various results of the studies have been presented.
However, assay systems for detecting the .beta.-amyloids easily and with high sensitivity have hitherto been scarcely reported, although deep interest has been expressed in the .beta.-amyloids. The sandwich enzyme immunoassay of the .beta.-amyloids is only reported by P. Seubert et al.,
The assay system of P. Seubert et al. is reported to have a detection sensitivity of 100 pg/ml, which is not satisfactory. Further, the assay system is reported to react also with a partial peptide consisting of However, a number of hydrophobic amino acids exist in C-terminal portions of the .beta.-amyloids, .beta.-amyloid (29-39), .beta.-amyloid (29-40), .beta.-amyloid (29-41), .beta.-amyloid (29-42) or .beta.-amyloid (29-43). This C-terminal region is therefore considered to be embedded in a cell membrane, and is assumed to play an important role in aggregation and deposition of peptides. For this reason, it i

REFERENCES:
Nature, vol. 359, pp. 322-325, 1992.
Seubert et al. "Insolation and quantification of soluble Alzheimers .beta.-peptide from biological fluids", Nature 359:325-327.
Morris et al "The Consortium to Establish a Registry for Alzheimer's Disease (CERAD)". Sep. 1989, Neurology, 39: 1159-1165.

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